کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2192307 1097887 2006 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Upregulation of mitochondrial respiratory complex IV by estrogen receptor-β is critical for inhibiting mitochondrial apoptotic signaling and restoring cardiac functions following trauma–hemorrhage
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Upregulation of mitochondrial respiratory complex IV by estrogen receptor-β is critical for inhibiting mitochondrial apoptotic signaling and restoring cardiac functions following trauma–hemorrhage
چکیده انگلیسی

Our recent study showed that estrogen receptor (ER) β plays a major role in mediating the salutary effects of 17β-estradiol (E2) on cardiac function following trauma–hemorrhage (T–H). E2 is known to regulate mitochondrial DNA (mtDNA)-encoded genes including the mitochondrial respiratory complex (MRC) proteins. Depressed MRC activity has been reported to promote the release of cytochrome c from mitochondria and induce apoptosis. We hypothesized that E2 and ERβ-mediated cardioprotection following T–H is dependent on mtDNA transcription encoding for MRC activity. To test this, male rats underwent T–H (mean BP 40 mm Hg ∼ 90 min, then resuscitation). During resuscitation, rats received either ERα agonist propylpyrazole triol (PPT; 5 μg/kg), ERβ agonist diarylpropionitrile (DPN; 5 μg/kg), E2 (50 μg/kg), or vehicle (10% DMSO). Another group of rats received mitochondrial respiratory complex-IV (MRC-IV) inhibitor sodium cyanide (SCN; 6 mg/kg) with or without DPN. The results indicated that 24 h after T–H, cardiac functions were depressed in the vehicle-treated but were normal in the DPN-treated rats. Moreover, E2 or DPN treatment after T–H normalized cardiac mitochondrial ERβ expression and increased mitochondrial ERβ DNA-binding activity. This was accompanied by an increase in MRC-IV gene expressions and activity, while MRC-I gene expression remained unchanged. Inhibition of MRC-IV in DPN-treated T–H rats by SCN abolished the DPN-mediated cardioprotection, ATP production, mitochondrial cytochrome c release, caspase-3 cleavage, and apoptosis. Thus, E2 and ERβ-mediated cardioprotection following T–H appears to be mediated via mitochondrial ERβ-dependent MRC-IV activity and inhibition of mitochondrial apoptotic signaling pathways.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 41, Issue 3, September 2006, Pages 511–521
نویسندگان
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